Figure 911

Mechanism of action of immunusuppressive drugs. A, The sites of action of the commonly used immunosuppressive drugs. Immuno-suppressive drugs interfere with allograft rejection at various sites in the rejection pathways. Glucocorticoids block the release of interleukin (IL)-1 by macrophages, cyclosporine (CsA) and FK506 interfere with IL-2 production from activated helper T cells, and azathioprine (AZA) and mycophenolate mofetil (MPA) prevent proliferation of cytotoxic and helper T cells.

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FIGURE 9-11 ( Continued)

B, Mechanism of action of CsA, FK506, and rapamycin (RPM). CsA and FK506 block the transduction of the signal from the T-cell receptor (TCR) after it has recognized antigen, which leads to the production of lymphokines such as IL-2, whereas RPM blocks the lymphokine receptor signal, eg, IL-2 plus IL-2 receptor (IL-2R), which leads to cell proliferation.

The addition of a prophylactic course of antithymocyte globulin (ATG) or OKT3 with delay of the administration of CsA or FK506 during the initial postoperative periods has been advocated by some groups. OKT3 prophylaxis was associated with a lower rate of early acute rejection and fewer rejection episodes per patient. Prophylactic use of these agents appears to be most effective in high-risk cadaver transplant recipients, including those who are sensitized or who have two HLA-DR mismatches or a prolonged cold ischemia time [2,10]. IFN-7—interferon gamma; TNF-a—tumor necrosis factor-a.

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